A pharmaceutical composition is disclosed, including: an interleukin-1 receptor antagonist, wherein the interleukin-1 receptor antagonist is a protein or a peptide; a buffer; and optionally one or more additional components each selected from the group consisting of a stabilizer and a tonicity modifier, wherein the pharmaceutical composition is adapted for administration via inhalation. Kits including the pharmaceutical composition of same and method of using same for treating an inflammatory disorder of lower airways in a human subject are also disclosed.

The human Interleukin 1 Receptor antagonist anakinra can be used in the treatment of pancreatic ductal adenocarcinoma (PDAC). The treatment involves administration of a daily dose of approximately at least 200 mg of anakinra to a patient in need thereof, for example to a patient who is undergoing a chemotherapy treatment regimen. The anakinra can be used in related treatment methods and corresponding pharmaceutical compositions.

The human Interleukin 1 Receptor antagonist anakinra can be used in the treatment of pancreatic ductal adenocarcinoma (PDAC). The treatment involves administration of a daily dose of approximately at least 200 mg of anakinra to a patient in need thereof, for example to a patient who is undergoing a chemotherapy treatment regimen. The anakinra can be used in related treatment methods and corresponding pharmaceutical compositions.

The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Methods are disclosed for treating an acute respiratory distress syndrome, such as an acute respiratory distress syndrome associated with a viral infection, such as SARS-CoV2 (COVID-19) in a subject in need thereof. These methods include administering to the subject a pharmaceutical preparation comprising isolated matrix bound vesicles (MBV) derived from extracellular matrix.

Methods are disclosed for treating an acute respiratory distress syndrome, such as an acute respiratory distress syndrome associated with a viral infection, such as SARS-CoV2 (COVID-19) in a subject in need thereof. These methods include administering to the subject a pharmaceutical preparation comprising isolated matrix bound vesicles (MBV) derived from extracellular matrix.

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

Disclosed herein are methods for treatment of a mesothelin (MSLN)-expressing cancer in a human subject comprising administration of, e.g., a plurality of anti-MSLN T cell receptor fusion protein (TFP)-expressing T cells. A ratio of CD4+ to CD8+ T cells in a sample from the human subject may have been determined before the administration of the plurality of anti-MSLN TFP-expressing T cells. The plurality of anti-MSLN TFP-expressing T cells may comprise a pre-determined ratio of CD4+ to CD8+ T cells.

A method treats a SARS-CoV-2 infection with anakinra. In particular the method treats or alleviates symptoms of respiratory distress and/or hyperinflammation in a patient. The treatment includes administering to a patient in need thereof a daily dose of at least about 400 mg of anakinra.